C(=O)([O-])[O-].[K+].[K+].S(C1C=CC(C)=CC=1)(O)(=O)=O.[CH2:18]([O:25][C:26](=[O:32])[C@H:27]([CH:29]([CH3:31])[CH3:30])[NH2:28])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.Br[CH2:34][C:35]1[CH:40]=[CH:39][C:38]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=2[C:47]#[N:48])=[CH:37][CH:36]=1.[Cl:49]CCl>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[ClH:49].[CH2:18]([O:25][C:26](=[O:32])[C@H:27]([CH:29]([CH3:30])[CH3:31])[NH:28][CH2:34][C:35]1[CH:36]=[CH:37][C:38]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=2[C:47]#[N:48])=[CH:39][CH:40]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1A mixture of potassium carbonate (152.2 g) and de-mineralized water (300 ml) was stirred for 10 to 15 minutes to dissolve the solid. The temperature of the mixture was maintained at 30° to 35° C. and dichloromethane (300 ml) was added. L-Valine benzyl ester tosylate (153.3 g), tetrabutyl ammonium bromide (10.0 g) and 4-bromomethyl-2′-cyanobiphenyl (100 g) were added to the reaction mixture. The reaction mixture was stirred for 20 to 24 hours at 30° to 35° C. After completion of the reaction de-mineralized water (400 ml) was added and the mixture was stirred for 5 minutes. The two phases were separated and the aqueous layer was extracted with dichloromethane (200 ml). The combined organic layer was washed with de-mineralized water (300 ml) and concentrated at 40° to 45° C. Ethyl acetate (600 ml) was then added to the residue and stirred for 5 to 10 minutes to dissolve the residue. The reaction mixture was cooled to 0° to 5° C. and concentrated hydrochloric acid (50 ml) was added to the reaction mixture. The mixture was stirred for 1 hour. The precipitated solid was filtered, washed with ethyl acetate and dried to obtain the title compound.
Wird geladen…